Aldehyde dehydrogenase
| Aldehyde dehydrogenase (NAD+) | |||||||||
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Monomer of human aldehyde dehydrogenase 2 (ALDH2) with a space-filling model of NAD+ in the active site.
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| Identifiers | |||||||||
| EC number | 1.2.1.3 | ||||||||
| CAS number | 9028-86-8 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
| Gene Ontology | AmiGO / EGO | ||||||||
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| Search | |
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| PMC | articles |
| PubMed | articles |
| NCBI | proteins |
Aldehyde dehydrogenases (EC 1.2.1.3) are a group of enzymes that catalyse the oxidation (dehydrogenation) of aldehydes. To date, nineteen ALDH genes have been identified within the human genome. These genes participate in a wide variety of biological processes including the detoxification of exogenously and endogenously generated aldehydes.
Aldehyde dehydrogenase is a polymorphic enzyme responsible for the oxidation of aldehydes to carboxylic acids, which leave the liver and are metabolized by the body’s muscle and heart. There are three different classes of these enzymes in mammals: class 1 (low Km, cytosolic), class 2 (low Km, mitochondrial), and class 3 (high Km, such as those expressed in tumors, stomach, and cornea). In all three classes, constitutive and inducible forms exist. ALDH1 and ALDH2 are the most important enzymes for aldehyde oxidation, and both are tetrameric enzymes composed of 54kDA subunits. These enzymes are found in many tissues of the body but are at the highest concentration in the liver.
The active site of the aldehyde dehydrogenase enzyme is largely conserved throughout the different classes of the enzyme and, although the number of amino acids present in a subunit can change, the overall function of the site changes little. The active site binds to one molecule of an aldehyde and an NAD(P)+ that functions as a cofactor. A cysteine and a glutamate will interact with the aldehyde substrate. Many other residues will interact with the NAD(P)+ to hold it in place. A magnesium may be used to help the enzyme function, although the amount it helps the enzyme can vary between different classes of aldehydes.
The overall reaction catalysed by the aldehyde dehydrogenases is:
In this NAD(P)+-dependent reaction, the aldehyde enters the active site through a channel located on the outside of the enzyme. The active site contains a Rossman fold, and interactions between the cofactor and the fold allow for the isomerization of the enzyme while keeping the active site functional.
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